Citation: Zhou J (2015) Comprehensive Reanalysis of Some Data in the Reports Relate to the TCR Vβ Repertoire of Peripheral Blood
in the Patients with Different Diseases. SOJ Immunol 3(2): 1-5. DOI: http://dx.doi.org/10.15226/soji/3/2/00124

Eighteen reports related to Variable region of Beta Chain (Vβ) of
T cell Receptors (TCR) of the patients with leukemia were reanalyzed.
In the results, Vβ3 and Vβ9 were the usually predominantly used
genes in all the diseases, which including infectious disease, cancers
and leukemia. There were common characteristic of TCR Vβ usage
in the same kind of disease; while there were specific characters in
the different individuals with the same disease. This finding indicated
that it may be helpful for the mechanism study or diagnosis of the
diseases according to the specific or common features of TCR Vβ
usage.

In the past fifteen years, there were some studies related to
the clonalities of TCR α and β heterodimer, especially the clonal
expression of Vβ genes. In these reports, the predominant usage
TCR Vβ gene families usually were shown, and these genes were
considered as the factors associated with the corresponding
diseases by the authors. However, there was no report about
an overview aiming at these reports till now. This paper just
focused on the reanalysis of the data in the reports. Through
this comprehensive analysis, we attempt to find some new ideas
which were different from the original authors, and exhibited
some novel indications for the researchers of this filed.

Generally, there were two Vβ genes which further divided
into two subfamilies in the family of 24 TCR Vβ genes: Vβ5 and
Vβ13. The former contained Vβ5.1 and Vβ5.2; the later had
Vβ13.1 and Vβ13.2. In some references of this study, there were
some Vβ genes else which held subfamilies, for example, Vβ7
contained Vβ7.1, Vβ7.2 and Vβ7.3. These differences probably
lied on the different classification standards for the subfamilies.
However, the main Vβ gene families’ classification was consistent
with each other. In order to unify the classification standard
and make the data convenient for counting the predominant
usage, the numbers of Vβ subfamilies were counted as the total
of the corresponding main Vβ gene family. Besides, a concept of
Predominant Usage Frequency (Frequencies) (PUF or PUFs) was
applied, and its calculation formula was as following:

PUF (%) = Σn/Σp × 100
Σn: the summary of the times for certain a Vβ gene which
was predominantly used; Σp: the summary of the patients with
certain disease or all the patients in the study.

Comprehensive Reanalysis

In the predominant usage Vβ genes of all the patients, Vβ3
were the highest usage genes, the PUF was 18% (36/200); Vβ9
was next to it with the PUF of 17% (34/200), which was followed
by Vβ5 with the PUF of 13% (26/200). Both PUFs of Vβ13 and
Vβ21 were 11.5% (23/200). In all of the 24 Vβ genes, the lowest
usage gene was Vβ4 with PUF of 1.5% (3/200); Vβ16 and Vβ24
were second to it and which PUFs were all 2.5% (5/200) (Figure
1).

As shown in Figure 2, in HBV infection, the gene with highest
PUF was Vβ11 (28%), Vβ12 was next to it with PUF of 22%.
The PUFs of Vβ8, Vβ9 and Vβ10 were all 16%; in HIV infection,
the gene with highest PUF was Vβ5 (37%), Vβ7 was next to it
in which PUF was 32%. The PUFs of Vβ9 and Vβ20 were both
26%. According to the predominant usage frequencies of TCR Vβ
specific to different diseases, the features of Complementarity Determining Region 3 (CDR3) of TCR Vβ were reanalyzed with
histograms.

Discussion

As the authors shown, there were different predominant usage
gene families in different diseases. For example, Vβ11 and Vβ12
expressed in HBV infection; Vβ3 and Vβ13 in CC; Vβ12, Vβ21 and
Vβ23 in APL; and so on. In most viewpoints of the researchers,
these different predominant usage genes were just specific to the
different diseases and probably represent the different features
of the corresponding diseases. However, in our opinion, there
were some insufficiencies in the perfect analysis for every report,
and there would be more meaning to comprehensively analyze
these research results.

In 24 Vβ gene families of all the cases, TCR Vβ3 was the
most advantageous usage gene in the diseases except HBV and
HIV infections. This probably indicated that Vβ3 always was the
predominantly used in most of diseases beside virus infections.
Vβ9 and Vβ13 even existed in all the diseases which except for
APL and AML, respectively. This result showed that there were
no specificities for their expression to the diseases; but if the
expression absence of the two genes could indicate the occurrence
of APL or AML needed for further study. As the gene families of
low PUFs, Vβ4 was predominantly used in HBV infection, CC
and APL; while Vβ16 was the advantageous expression gene for
HBV infection, AML and CML. These results showed that Vβ4 and
Vβ16 probably were the diagnosis indices for HBV, CC, APL, AML
and CML; especially, Vβ4 plus Vβ16 may be more helpful for the
diagnosis of HBV infection because both had relative high PUFs
in this disease.

According to different PUFs of TCR Vβ in different diseases, the histograms were designed. As Figure 2 shown, the columns of
different heights in the histogram represented the predominant
usage frequencies of Vβ subfamilies. Obviously, the panorama
of each histogram looked like a key, and the prominent columns
were as same as the kits of the key. There were different kits in
different diseases, for example, the components of the kits for
HBV infection were Vβ2-Vβ4-Vβ5-Vβ8-Vβ9-Vβ10-Vβ11-Vβ12-
Vβ13-Vβ15-Vβ16-Vβ17- Vβ18-Vβ21-Vβ22-Vβ23-Vβ24; those
were Vβ5-Vβ7-Vβ9-Vβ13-Vβ20 in HIV infection; while those
were Vβ2-Vβ7-Vβ9-Vβ21 in AMOL. Except for the components,
and the height of the column determined by PUF was also
the factor which determined the key’s feature. The higher the
frequency of the TCR Vβ gene family was, the higher the kit of the
key would be. Therefore, to some extent, the key presented the
total characterization of TCR Vβ skewness of the patients with
certain a disease. As we known, the skewness of TCR Vβ specific
to the associated antigen of the corresponding disease, so the key
formed with the predominant usage genes could be taken as the
whole skewness of TCR Vβ; in another words, it was a specific
key to the certain a disease. There is a proverb in China which
says that ‘Open different locks with different keys’. Accordingly,
there should be a key specific to every disease, such as various
pathogen infections, colorectal cancer, leukemia, and so on.

Conclusion

Through the reanalysis of the data in the articles related
to TCR Vβ predominant usage, we found the total usage
characteristics of 24 Vβ gene families in the different diseases,
and the individual features of the gene usage in each of the
disease. To our understanding, these results probably pose a new
idea or a novel viewpoint for analyzing and using the skewness
of TCR for the researchers. For example, if the histogram of TCR

In all the patients, Vβ3 were the highest usage genes, the PUF was 18% (36/200); Vβ9 was next to it with the PUF of 17% (34/200), which was followed
by Vβ5 with the PUF of 13% (26/200). Both PUFs of Vβ13 and Vβ21 were 11.5% (23/200). In all of the 24 Vβ genes, the lowest usage gene was
Vβ4 with PUF of 1.5% (3/200); Vβ16 and Vβ24 were second to it and which PUFs were both 2.5% (5/200).

Figure 1:
The total predominant usage frequencies of TCR Vβ genes summed from the patients with different diseases.

According to the reports relates to the predominant usage frequencies of TCR Vβ specific to different diseases, the features of Complementarity Determining
Region 3 (CDR3) of TCR Vβ were reanalyzed with histograms respectively. The columns with different heights represent different predominant
usage frequencies of Vβ subfamilies (including the monoclonal, biclonal and oligoclonal gene families), and the polyclonal and low-expression
genes are ignored in this analysis. It is easy to see that each merged gram likes a big key, which probably reflects the characteristics of the skewness of
T Cell Receptor (TCR) specific to the corresponding disease. (A) The TCR key to Hepatitis Virus B (HBV) infection; (B) The TCR key to Human Immunodeficiency
Virus (HIV) infection; (C) The TCR key to Pemphigus vulgaris; (D) The TCR key to colorectal cancer; (E) The TCR key to lung cancer; (F) The
TCR key to acute promyelocytic leukemia; (G) The TCR key to T cell-acute lymphoblastic leukemia; (H) The TCR key to B cell-acute lymphoblastic leukemia
; (I) The TCR key to acute monoblastic leukemia; (J) The TCR key to acute myelogenous leukemia; (K) The TCR key to chronic myeloid leukemia.

Figure 2:
The different "keys" specific to different disease formed with the predominant usage frequencies of TCR Vβ genes in PBMC of the corresponding
patients.

Table 1: The summary of the predominant usage TCR Vβ genes in PBMC of all the patients with different diseases extracted from the references.

Vβ of a patient looks like that of AMoL, this may be helpful for the
physician to make a diagnosis; and if the heights of predominant
columns decrease, this may, indicate that the treatment is proper
for the patient in clinic. Of course, this hypothesis needs lots of
studies to prove by the researchers in future.

Acknowledgements

The work is supported by the Provincial Science and
Technology Development Project (No. 2012YD180540), the
Provincial Nature Science Foundation (No. ZR2012HL29), the
Project of Shandong Province Higher Educational Science and
Technology Program (No. J11LF18), the Population and Family
Planning Commission (No. (2011)13), and the Development Plan
Project of Jining Science and Technology Bureau of Shandong
Province (No. (2011) 57, 2014jnjc12 and 2014jnyx14).